Performance of a single assay for both type III and type VI TMPRSS2:ERG fusions in noninvasive prediction of prostate biopsy outcome.
BACKGROUND
TMPRSS2:ERG fusions are promising prostate cancer biomarkers. Because they can occur in multiple forms in a single cancer specimen, we developed a quantitative PCR test that detects both type III and type VI TMPRSS2:ERG fusions. The assay is quantified from a standard curve determined with a plasmid-cloned type III TMPRSS2:ERG fusion target.


METHODS
We collected expressed prostatic secretion (EPS) under an institutional review board-approved, blinded, prospective study from 74 patients undergoing transrectal ultrasound-guided biopsy for prostate cancer. We compared the characteristic performance of the test for type III and type VI TMPRSS2:ERG fusions in predicting biopsy outcome and distinguishing between high and low Gleason scores with similar tests for the expression of PCA3 and DNA methylation levels of the APC, RARB, RASSF1, and GSTP1 genes. We used logistic regression to analyze the effects of multiple biomarkers in linear combinations.


RESULTS
Each test provided a significant improvement in characteristic performance over baseline digital rectal examination (DRE) plus serum prostate-specific antigen (PSA); however, the test for type III and type VI TMPRSS2:ERG fusions yielded the best performance in predicting biopsy outcome [area under the curve (AUC) 0.823, 95% CI 0.728-0.919, P < 0.001] and Gleason grade >7 (AUC 0.844, 95% CI 0.740-0.948, P < 0.001).


CONCLUSIONS
Although each test appears to have diagnostic value, PSA plus DRE plus type III and type VI TMPRSS2:ERG provided the best diagnostic performance in EPS specimens.
Clark
Jarrod P
JP
Kaplan Clinical Research Laboratory, City of Hope, Duarte, CA 91010-3000, USA.
Munson
Kristofer W
KW
Gu
Jessie W
JW
Lamparska-Kupsik
Katarzyna
K
Chan
Kevin G
KG
Yoshida
Jeffrey S
JS
Kawachi
Mark H
MH
Crocitto
Laura E
LE
Wilson
Timothy G
TG
Feng
Ziding
Z
Smith
Steven S
SS
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000368:Aged; D000951:Antigens, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D001706:Biopsy; D019175:DNA Methylation; D014644:Genetic Variation; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D018168:Receptors, Retinoic Acid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics; D014463:Ultrasonography
D025601:Adenomatous Polyposis Coli Protein; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; C411762:RASSF1 protein, human; D018168:Receptors, Retinoic Acid; C515553:TMPRSS2-ERG fusion protein, human; D025521:Tumor Suppressor Proteins; C479341:prostate cancer antigen 3, human; C082925:retinoic acid receptor beta; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D017430:Prostate-Specific Antigen